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Unidad de Investigación Clínica de Oncohematología Pediátrica IdiPAZ-CNIO. / Laura M. Lombardía. CNIO
At the Spanish National Cancer Research Center (CNIO), the IdiPAZ-CNIO Pediatric Oncohematology Joint Clinical Research Unit, headed by oncologist Antonio Pérez, works to ensure that children and teenagers with cancer are not left out of personalized immunotherapies.
CAR-T therapies have been effective in 60% of the pediatric patients who have received them; “we study why they have not worked in the rest,” explain CNIO researchers Cristina Aguirre and Andrés París.
International Childhood Cancer Day is February 15.
Pediatric cancer is relatively rare, yet it is the leading cause of death by disease in children and teenagers in the developed world. It is different from adult cancer and therefore requires research and specific therapies. But for pediatric patients treatments are not improving at the same rate as for the rest, recalls Antonio Pérez-Martínez, head of the IdiPAZ-CNIO Pediatric Oncohematology Joint Clinical Research Unit.
His group at the CNIO is doing research so that children and teenagers are not left out of personalized immunotherapies, which are more effective and have fewer side effects. While these therapies, such as those called CAR-T, are used in an increasing number of adult cancers, “to date, only one type of cancer in the pediatric population, type B lymphoblastic leukemias, benefits from this therapeutic strategy,” says Pérez-Martínez.
Delay in immunotherapies for children with cancer
Every year, 35,000 pediatric cancer patients are diagnosed in Europe, some 1.500 of them in Spain, according to the Spanish Association of Pediatrics. Around 80% are cured. However, pediatric cancer treatments today are largely the same as they were decades ago, very toxic and with a risk of sequelae, “something especially important in patients with many years of life ahead of them,” points out Pérez-Martínez.
Why is progress not being made at the same rate?
The low incidence of childhood cancer limits its commercial interest, says the European Society of Pediatric Oncology. This society has already warned of the need to change a regulatory system that slows down access to advanced immunotherapies for pediatric cancer patients.
The role of industry and academia
For Pérez-Martínez, among the reasons for this situation is “the intrinsic difficulty in conducting prospective multicenter clinical studies in pediatric patients with such complex and not very prevalent pathologies”, as well as “the scant interest of the pharmaceutical industry in financing these clinical studies, given the low prevalence, high complexity and low expected return”.
European oncologists have indeed stated that “the development of CAR T-cell products for the pediatric cancer population by pharmaceutical companies is unlikely to return investments, and thus, it is doubtful that this path of approval will lead to access of effective products to patients.” These experts call “for a concerted academic action, complementing the pharmaceutical industry, to develop the field”.
New CAR-Ts for pediatric cancer at the CNIO
CAR-T therapies have been effective in 40% of the paediatric patients who have received them, and “we are investigating why they have not worked in the rest,” explain Cristina Aguirre and Andrés París, from the IdiPAZ-CNIO Paediatric Oncohematology Clinical Research Unit.
CAR-T therapies are based on modifying the patient’s own defensive cells, lymphocytes, to enable them to target and destroy tumor cells. The lymphocytes are removed from the patient and re-infused once they have been modified.
But sometimes lymphocytes from patients cannot be used. The CNIO group wants to overcome this obstacle by using donor lymphocytes, i.e. to develop ‘universal donor’ CAR-T cells that do not generate rejection in the patient.
CAR-T with iron nano-particles
Another line seeks to extend the effectiveness of CAR-T to solid tumors. “So far CAR-Ts have been successful mostly in blood tumors. Solid tumors develop natural barriers to prevent defensive cells from entering,” explains Paris.
His strategy is to bypass these barriers by using iron nanoparticles, which are guided into the tumor by an external magnetic field. It is a collaboration with the National Center for Biotechnology and the Institute of Material Sciences in Madrid.
Cancer is personal, so is therapy
Another challenge is the heterogeneity of tumors: each cancer has its unique features in each patient, which means that treatments need to be much more personalized. CNIO researcher Adriana Mañas develops animal models that reproduce the tumor of specific patients, to test the success of possible therapies before administering them.
“With our research we seek to solve the problems that arise in the clinic,” says París. This is a multidisciplinary task in which, in addition to oncologists and biologists, mathematics plays a key role. Odelaisy León researches in mathematical oncology to transform the large amount of data generated by CNIO research into relevant information.
In addition, the pediatric cancer unit collaborates with the CNIO Chromosome Dynamics Group, led by Ana Losada, which studies Ewing’s sarcoma. This group has recently discovered an alteration in the most aggressive cases of this sarcoma, a bone and soft tissue tumor that occurs in children and young adults.